Transvascular nerve stimulation apparatus and methods

ABSTRACT

The invention, in one aspect, relates to an intravascular electrode system. The system comprises one or more electrodes supported on an elongated resiliently flexible support member, and the support member may be used to introduce the electrodes into a blood vessel. As the support member is introduced into the blood vessel the support member bends to follow the path of the blood vessel.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/383,285, filed Sep. 5, 2014, which is a 371 national stageapplication of PCT Patent Application No. PCT/CA2013/050159, filed Mar.4, 2013, which claims priority from U.S. Provisional Patent ApplicationNo. 61/606,899, filed Mar. 5, 2012. The entirety of each of the aboveapplications is incorporated herein by reference.

TECHNICAL FIELD

The invention relates to neurophysiology and in particular to apparatusand methods for stimulating nerves through the walls of blood vessels.Non-limiting embodiments include nerve stimulation apparatus, electrodestructures, electrodes and related methods.

BACKGROUND

Nerve stimulation can be applied in the treatment of a range ofconditions. Nerve stimulation may be applied to control muscle activityor to generate sensory signals. Nerves may be stimulated by surgicallyimplanting electrodes in or near the nerves and driving the electrodesfrom an implanted or external source of electricity.

The phrenic nerves normally carry signals that cause the contractions ofthe diaphragm that are necessary for breathing. Various conditions canprevent appropriate signals from being delivered to the phrenic nerves.These include:

-   -   chronic or acute injury to the spinal cord or brain stem;    -   Amyotrophic Lateral Sclerosis (ALS);    -   disease affecting the spinal cord or brain stem; and,    -   decreased day or night ventilatory drive (e.g. central sleep        apnea, Ondine's curse). These conditions affect a significant        number of people.

Mechanical ventilation (MV) may be used to help patients breathe. Somepatients require chronic mechanical ventilation and many more patientsrequire temporary mechanical ventilation. Mechanical ventilation can belifesaving but has a range of significant problems and/or side effects.Mechanical ventilation:

-   -   tends to provide insufficient venting of the lungs. This can        lead to accumulation of    -   fluid in the lungs and susceptibility to infection and        pneumonia.    -   requires apparatus that is not readily portable.    -   can adversely affect venous return because the lungs are        positively pressurized.    -   interferes with eating and speaking.    -   requires costly maintenance and disposables.    -   tends to cause positive pressure ventilator induced lung injury        (VILI) and ventilator associated pneumonia (VAP).

A patient on mechanical ventilation is tied to a ventilator, and doesnot breathe independently. This can lead to atrophy of the diaphragmmuscle (ventilator induced diaphragmatic dysfunction; VIDD) and anoverall decline in well being. Muscle atrophy can occur surprisinglyrapidly and can be a serious problem. In patients on mechanicalventilation, the central respiratory drive of the diaphragm issuppressed. The inactivity of the diaphragm muscle causes rapid disuseatrophy. According to a published study (Levine et al., New EnglandJournal of Medicine, 358: 1327-1335, 2008), the diaphragm muscle couldshrink by 52-57% after just 18-69 hours of mechanical ventilation andsedation. Ventilator-induced diaphragm atrophy could cause a patient tobecome ventilator-dependent. Patients in intensive care units (ICU) whobecome dependent on mechanical ventilation (MV) are at high risk ofcomplications such as ventilator-acquired pneumonia (VAP) and nosocomialinfections and are seven times more likely to die in the ICU. It hasbeen reported that in 2008, 1.58 million ICU patients in the UnitedStates require MV every year, of which 20-30% (about 400,000mechanically ventilated patients) have difficulty weaning from MV andare at risk of becoming ventilator-dependent.

Three methods have been used to reverse or slow down atrophy in disuseddiaphragm muscles by stimulating the phrenic nerves and are discussedbelow.

Method 1. Phrenic nerve pacing uses electrodes implanted in the chest todirectly stimulate the phrenic nerves. The Mark IV Breathing PacemakerSystem available from Avery Biomedical Devices, Inc. of Commack, N.Y.,USA, is a diaphragmatic or phrenic nerve stimulator that has surgicallyimplanted receivers and electrodes mated to an external transmitter byantennas worn over the implanted receivers. Implanting electrodes andother implantable components for phrenic nerve pacing requiressignificant surgery. The surgery is risky and complicated by the factthat phrenic nerves are thin (approximately 2 mm in diameter) anddelicate. The surgery involves significant cost.

Method 2. Laproscopic diaphragm pacing developed by biomedical engineersand physician researchers at Case Western Reserve University is anothertechnique for controlling breathing. Laproscopic diaphragm pacinginvolves placing electrodes at motor points of the diaphragm.

Method 3. A method using intravascularly implanted electrodes tostimulate a nerve has been developed by Joaquin Andres Hoffer and isdescribed in U.S. patent application Ser. No. 12/524,571 (published onFeb. 11, 2010 as US2010/00336451) entitled “Transvascular NerveStimulation Apparatus And Methods”, which is hereby incorporated byreference.

Method 3 has advantages over Methods 1 and 2, because it does notrequire invasive surgery that would typically be performed under fullanaesthesia. Furthermore, ICU patients are not typically eligible forMethods 1 and 2.

There remains a need for cost-effective, practical, surgically simpleand minimally invasive apparatus and methods for nerve stimulation.There is also a need for apparatus and methods for facilitating patientson MV to breathe more naturally and to be weaned from MV. There is alsoa need for cost effective, practical apparatus and methods forinstalling and/or removing nerve stimulation apparatus.

SUMMARY OF THE INVENTION

This invention has a number of aspects. Aspects of the inventioninclude: designs for intravascular electrodes; electrode structures;nerve stimulation apparatus; intravascular apparatus includingelectrodes and structures for introducing and supporting the electrodes;catheters equipped with electrodes; methods for nerve stimulation; andmethods for measuring the location of an electrode structure within ablood vessel relative to a target nerve. While these and other aspectsmay be applied together, individual aspects may be applied separately aswell as in other combinations and contexts. For example, electrodestructures as described herein may be applied in combination withvarious deployment systems known in the art for various diagnosticand/or therapeutic applications.

Aspects of the invention may be applied for restoring breathing,treating conditions such as muscle atrophy, chronic pain, and other usesinvolving nerve stimulation. Aspects of the invention may be applied inthe treatment of acute or chronic conditions. Aspects of the inventionmay be applied to conveniently deploy and remove electrode structures ina patient.

One aspect of the invention relates to transvascular stimulation ofnerves. In transvascular stimulation, suitable arrangements of one ormore electrodes are positioned in a blood vessel that passes close to anerve to be stimulated. Electrical currents pass from the electrodesthrough a wall of the blood vessel to stimulate the target nerve.

One aspect of the invention relates to transvascular stimulation ofnerves in the neck and chest of a human or other mammals (e.g., a pig).FIG. 1A illustrates the anatomy of selected nerves and blood vessels inthe neck and chest of a human and, in particular, the relative locationsof the left and right phrenic nerves (PhN), vagus nerves (VN), internaljugular veins (UV), brachiocephalic veins (BCV), superior vena cava(SVC) and left subclavian vein (LSV).

Further aspects of the invention and features of example embodiments areillustrated in the appended drawings and/or described in the text ofthis specification and/or described in the accompanying claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings illustrate non-limiting example embodiments ofthe invention.

FIG. 1A illustrates the anatomy of selected nerves and blood vessels ina person's neck and upper torso.

FIGS. 2A-2D are schematic views of a nerve stimulation apparatusaccording to an example embodiment of the invention.

FIGS. 3A-3C illustrate the operation of nerve stimulation apparatus.

FIG. 4A illustrates a shaft portion comprising a pair of attached tubes.

FIG. 4B illustrates a shaft portion comprising telescoping tubes.

FIGS. 5A and 5B are schematic views of a nerve stimulation apparatusaccording to an example embodiment of the invention.

FIGS. 6A and 6B are schematic views of a nerve stimulation apparatusaccording to another example embodiment of the invention.

FIGS. 7A and 7B are schematic views of a nerve stimulation apparatusaccording to another example embodiment of the invention.

FIG. 8 schematically shows a nerve stimulation apparatus according toanother example embodiment of the invention.

FIG. 9 schematically shows a nerve stimulation apparatus according toanother example embodiment of the invention.

FIG. 10A is a side view of a nerve stimulation apparatus according toanother example embodiment of the invention. FIG. 10B is an isometricview of the apparatus of FIG. 10A in combination with an introducer anda hub. FIGS. 10C and 10D are examples of alternative cross-sectionalviews of the apparatus of FIG. 10A.

FIGS. 11A and 11B show a nerve stimulation apparatus in combination withan introducer and a hub according to an example embodiment of theinvention. FIGS. 11C and 11D are cross sectional views of nervestimulation apparatus along lines B-B and A-A respectively shown in FIG.11B.

FIG. 12 shows a nerve stimulation apparatus according to an exampleembodiment of the invention.

FIG. 13A shows a nerve stimulation apparatus according to an exampleembodiment of the invention that provides a five-lumen catheter. FIGS.13B-13E show some possible cross sections of the apparatus of FIG. 13Ataken at line A-A in FIG. 13A.

FIG. 14A shows another embodiment of a nerve stimulation apparatus.FIGS. 14B and 14C show some possible cross sections of a tubular memberof the apparatus of FIG. 14A.

FIG. 15 shows a nerve stimulation apparatus.

FIG. 16 shows a nerve stimulation apparatus.

FIG. 17 shows a nerve stimulation apparatus.

FIGS. 18A, 18B show an electrode structure according to an exampleembodiment of the invention. FIG. 18A is a top plan view of theelectrode structure. FIG. 18B is a bottom perspective view of theelectrode structure.

FIG. 19A shows a schematic of a cross section of an electrode structureaccording to one example embodiment of the invention. FIG. 19B showsdetails electrodes of the electrode structure of FIG. 19A.

FIGS. 20A and 20B are perspective and side views of an electroderetaining wire according to one example embodiment.

FIGS. 21A, 21B are top and bottom perspective views of an electrodestructure.

FIG. 22 shows an electrode structure according to one exampleembodiment.

FIGS. 23A-23E show how an example electrode structure may be rolled upand retracted into a tubular member.

FIGS. 24A-24E show how an example electrode structure may be rolled up,deployed, and retracted into a tubular member.

FIGS. 25 and 26 show two example electrode structures.

FIGS. 27A-27E schematically illustrate a nerve stimulation apparatusaccording to another embodiment.

FIGS. 28A, 28B show an example method for locating an electrodestructure in a blood vessel V to stimulate a target nerve.

FIGS. 29A-29H, 29L-29Q, and 30A-30H show various sensors which may beused with the nerve stimulation apparatus described herein as well as inother contexts.

FIGS. 31A to 31E shows an example shroud design which may be used withthe nerve stimulation apparatus described herein as well as in othercontexts.

DETAILED DESCRIPTION

Throughout the following description, specific details are set forth inorder to provide a more thorough understanding of the invention.However, the invention may be practiced without these particulars. Inother instances, well-known elements have not been shown or described indetail to avoid unnecessarily obscuring the invention. Accordingly, thespecification and drawings are to be regarded in an illustrative, ratherthan restrictive.

Apparatus according to some embodiments provides intravascular electrodesystems which include one or more electrodes supported on an elongatedresiliently flexible support member. The support member may be used tointroduce the electrodes into a blood vessel. As the support member isintroduced into the blood vessel the support member bends to follow thepath of the blood vessel. Restoring forces resulting from the resilienceof the support member hold the one or more electrodes in place againstthe wall of the blood vessel. The electrode structure may compriseflexible electrically insulating pads that insulate electrodes frombeing in direct contact with blood in the main passage of the bloodvessel.

In some embodiments the apparatus includes two or more electrodes atspaced-apart locations along the support member. Spacing between theelectrodes may be selected to allow the electrodes to be locatedproximate to anatomical structures, for example nerves passing nearbythe blood vessel. In an example embodiment, electrodes are spaced aparton a support structure and oriented so that an intravascular electrodesystem may be placed with electrodes located to stimulate a patient'sleft and right phrenic nerves. The electrodes may optionally havedifferent circumferential orientations with respect to a longitudinalcenterline of the support structure.

In some embodiments the support member is more flexible in one directionthan in another. This can help to preserve a desired orientation ofelectrodes while the electrode system is being introduced into a bloodvessel.

In some embodiments the electrode system comprises a catheter having oneor more lumens. The catheter may provide the functionality of a centralcatheter of the type commonly used in intensive care units, for example.Such embodiments provide the advantage of electrodes that may beapplied, for example, for stimulating nerves (e.g. for diaphragm pacing)and/or for monitoring electrical activity in the body of a patient inthe same package as a central catheter that may be required in anyevent. In some embodiments, the catheter also serves as a supportstructure as described above.

Some embodiments comprise electrode structures comprising electrodes andasymmetrical electrically-insulating backing sheets. The backing sheetscan electrically isolate the electrodes from blood in the lumen of ablood vessel, thereby allowing more efficient stimulation ofextravascular structures such as nearby nerves. The asymmetricalarrangement of the backing sheet allows the backing sheet to be rolledinto a compact configuration for insertion of the electrode structureinto a blood vessel while providing a backing sheet that can provideelectrical insulation for two or more electrodes. In some embodimentsthe backing sheet has a generally trapezoidal configuration. The backingsheet may be formed so that it tends to unroll from the rolledconfiguration. The backing sheet may be formed with a natural curvaturesimilar to that of a wall of a blood vessel against which the backingsheet will be deployed. The backing sheet may be but need not becompletely electrically insulating. Such a backing sheet can beadvantageous as long as it provides a resistance to the flow ofelectricity substantially greater than the resistance that would beprovided by blood in the blood vessel in the absence of the backingsheet. Such electrode structures may be applied in a wide range ofintravascular applications.

Some embodiments provide electrode structures that include a retainerthat holds a backing sheet in place. The retainer may comprise, forexample, a formed piece of wire that extends through apertures in thebacking sheet. In some embodiments the retainer comprises a pair of wiresections, which may be generally parallel, that are each woven throughapertures in the backing sheet. Distal ends of the wire sections may bejoined. The wire sections may be parts of a continuous wire. Distal endsof the wire sections may be bent back over the backing sheet. In someembodiments the retainer is electrically conductive and may be appliedas one electrode, for example a reference electrode for electricalmeasurements and/or one of two or more electrodes for delivery ofstimulation. The backing sheet may be rolled around the retainer forintroduction into a blood vessel. Such electrode structures may beapplied in a wide range of applications.

Some embodiments provide electrode structures in which a backing sheetfor one or more electrodes is provided by a wall of an inflatablestructure. The structure may be inflated to hold the electrodes againsta wall of a blood vessel. The structure may, for example, be located ona side of a catheter or other support member. In some embodiments,inflation of the inflatable structure actuates a backing member carryingone or more electrodes to move toward engagement with a wall of a bloodvessel.

Some embodiments provide intravascular electrode structures on which oneor more electrodes is supported on a support member which includeintegrated position-measurement transducers for measuring a displacementof an electrode along a blood vessel into which the electrode is beinginserted. The apparatus, including the position-measurement transducersmay be intended to be disposable after a single use. Various embodimentsof example position measurement transducers that can provide accurateposition measurement in a suitable form factor and/or may be fabricatedinexpensively are described below.

The following description describes examples of nerve stimulationapparatus and components suitable for application in nerve stimulation.In some cases the examples given are adapted for stimulation of phrenicnerves in a human or other mammals. The nerve stimulation apparatusdescribed herein has a number of features which are particularlyadvantageous in combination with one another but can also be usedindividually, in other combinations, or in combination with the featuresdescribed in US2010/00336451.

FIGS. 2A-2C are schematics of a nerve stimulation apparatus 10 accordingto an example embodiment of the invention. Nerve stimulation apparatus10 comprises electrode structures 12A, 12B (collectively 12). Nervestimulation apparatus 10 also comprises a tubular member 24. Tubularmember 24 may be a catheter or cannula-type tubular member. For example,tubular member 24 may be a central venous catheter. Tubular member 24 iscapable of being inserted into a lumen of a blood vessel.

Tubular member 24 has a distal end 26, a proximal end 28, an outer wallor sheath 30 that extends from distal end 26 to proximal end 28. Tubularmember 24 may comprise one or more internal lumens (not specificallyindicated in FIGS. 2A-2C—examples of such lumens are shown in otherFIGS.) For example, tubular member 24 may be a multi-lumen catheter.

In the example embodiment, at least one lumen extends longitudinallyfrom proximal end 28 to distal end 26. The lumens may have exit openingson wall 30 of tubular member 24. These openings may be spaced apartalong the length of tubular member 24. The lumens may be used forremoving blood samples, inserting medication, delivering fluids ornutrients, measuring chemical or physical parameters in blood, such aspH or temperature, and the like. For example, agents may be appliedthrough one or more of the openings to prevent clot formation onelectrode structures 12. In FIG. 2A, an example opening 34 is shown,which provides an exit port for electrode structure 12B. Opening 34 maybe upstream from electrode structure 12B relative to a direction ofblood flow in a blood vessel in which nerve stimulation apparatus 10 isdeployed.

Tubular member 24 may be flexible. A range of materials may be used forconstruction of tubular member 24, including silicone, polyurethane, orother suitable polymers, stainless steel, and the like. Tubular member24 may have markings for length determination. In some embodiments,tubular member 24 is more flexible in one bending direction than inanother bending direction. In some embodiments, different sections oftubular member 24 have different levels of flexibility. For example, thedistal part of tubular member 24 may be more flexible than the proximalpart of tubular member 24.

Electrode structure 12A is positioned at or near distal end 26 oftubular member 24. Electrode structure 12B is positioned at amid-portion of tubular member 24. Electrode structures 12A, 12B aremovable between a retracted position (i.e., received in tubular member24) and a deployed position (i.e., extending out of tubular member 24).When electrode structures 12A, 12B are in a retracted position,electrode structures 12A, 12B are located inside or mostly insidetubular member 24 (FIG. 2A). When electrode structure 12A, 12B are in adeployed position, electrode structure 12A extends out of a distalopening of tubular member 24, and electrode structure 12B extends out oftubular member 24 from an opening 34 on wall 30 (FIGS. 2B and 2C).Typically, electrode structure 12 is dimensioned so that, when in adeployed position inside a blood vessel, it will extend approximately45° to 60° of the way around a wall of the blood vessel, although thisis not mandatory.

In FIGS. 2A-2C, a representative electrode 20 is shown for eachelectrode structure 12. However, it should be noted that each electrodestructure 12 may comprise a plurality of electrodes. For example, one ormore electrodes may be used for stimulating a target nerve; and one ormore additional electrodes may be used for ECG monitoring. In someembodiments, one electrode may function as a cathode and anotherelectrode may function as an anode. Electrode structure 20 alsocomprises an insulating pad 42.

Each electrode structure 12 may be coupled to an elongated flexibleshaft portion 14 which extends inside tubular member 24. Shaft portion14 is not directly visible in FIGS. 2A-2C, but FIG. 2D schematicallyshows a shaft portion 14 coupled to electrode 12A, without tubularmember 24. In FIG. 2D, elongated flexible shaft portion 14 has a distalend 16 and a proximal end 18. Electrode structure 12A is coupled todistal end 16 of shaft portion 14. Shaft portion 14 may comprise, forexample, a single wire or tube or a plurality of wires or tubes. Shaftportion 14 may comprise one or more suitable leads (not specificallyindicated in FIG. 2D, as leads may be hidden inside shaft portion 14)which may electrically couple one or more electrodes 20 to an apparatusfor monitoring electrical activity and/or delivering electricalstimulation by way of electrodes 20. The leads and the electrodes 20 maybe electrically coupled in a one-to-one relationship such that eachelectrode 20 is individually addressable. In some embodiments, somegroups of two or more electrodes 20 are connected to a common lead. Theleads may be carried in or along shaft portion 14.

At equilibrium, shaft portion 14 may have a configuration that isstraight or curved. Shaft portion 14 may have an initial radius ofcurvature greater than a radius of curvature of the left brachiocephalicvein (BCV) and superior vena cava (SVC) into which nerve stimulationapparatus 10 may be introduced. Shaft portion 14 may be resilient andtending to return to its original configuration; thus, distal end 16 ofshaft portion 14 tends to spring toward the far wall of the superiorvena cava (SVC) when nerve stimulation apparatus 10 is inserted in apatient from the left side of the body (e.g., from LSV into BCV andSVC). This is convenient because the right phrenic nerve typically runsalongside the far wall of the superior vena cava (SVC) at this point.

In some embodiments, shaft portion 14 is more flexible in one directionthan in another direction. For example, shaft portion 14 may be orientedsuch that it is easier to bend downwardly than sideways. Thisfacilitates insertion and positioning of shaft portion 14 in SVC whichextends downwardly from the BCV.

In some embodiments, different parts of shaft portion 14 have differentlevels of flexibility. For example, the distal part of shaft portion 14may be more flexible than the proximal part of shaft portion 14. In someembodiments, flexibility of the shaft portion may vary along the lengthof the shaft portion. Shaft portion 14 may be made of stainless steel orother suitable material (e.g., Nitinol, high-density plastics,elastomers etc.). In some embodiments shaft portion 14 comprises a pairof flexible stainless steel tubes that are attached together by, forexample, welding.

The operation of nerve stimulation apparatus 10 is schematically shownin FIGS. 3A-3C. Nerve stimulation apparatus 10 may be inserted into aperson's subclavian vein and SVC as follows. The electrode structures12A, 12B are initially located within tubular member 24. A percutaneouspuncture is made into the patient's LSV. Tubular member 24 is theninserted through the puncture into the LSV. Such insertion could be doneunder local anaesthesia. General anaesthesia is typically not required.Tubular member 24 of nerve stimulation apparatus 10 is then advancedinto the patient's left BCV and eventually into SVC. Care should betaken not to advance tubular member 24 into the right atrium of theheart. When the distal portion of tubular member 24 reaches the SVC, thedistal portion of tubular member 24 bends downwardly. Electrodestructures 12A, 12B are moved from a retracted position (FIG. 3B) to adeployed position (FIG. 3C). Electrode structures 12A, 12B arepositioned adjacent the left and right phrenic nerves. As describedbelow, monitoring may be performed during insertion to locate theelectrode positions which allow for most effective stimulation of thephrenic nerve.

In the deployed position, electrode structures 12A, 12B extend out oftubular member 24. Electrodes 20 are pressed against a wall of the bloodvessel, whereas the insulating pads 42 of the electrode structures 12A,12B prevent the electrodes 20 from being in close electrical contactwith the bulk of the blood flowing through the blood vessel. Thecurvature of nerve stimulation apparatus 10 may conform to the curvatureof the patient's left BCV and SVC. The two electrode structures 12A, 12Bmay be arranged roughly at 90° to one another about the longitudinalaxis of nerve stimulation apparatus 10, with electrode structure 12Aoriented toward the right phrenic nerve and electrode structure 12Boriented toward the left phrenic nerve.

Testing may be done to locate electrode structures 12A, 12B at desiredpositions relative to the left and right phrenic nerve. Methods forlocating an electrode structure relative to a target nerve are describedbelow herein (see FIGS. 28A, 28B). Measurements can also be made todetermine which electrode or electrodes of an electrode structurecomprising multiple electrodes most effectively stimulate the targetnerve.

Once nerve stimulation apparatus 10 has been properly inserted into apatient as described above, electrodes 20 are electrically coupled to astimulation device (e.g., a pulse generator which may be optionallylocated outside the body) to apply electric current to the phrenicnerves, causing the diaphragm muscle to contract. The contraction of thediaphragm muscle causes inhalation of air into the lungs. When theelectric stimulation of the phrenic nerves is stopped, the diaphragmmuscle relaxes and exhalation occurs. This allows the patient to breathemore naturally. Nerve stimulation apparatus 10 may be used incombination with a control unit (e.g., a bedside control unit).

Nerve stimulation apparatus 10 may be removed from the patient's body.During removal, electrode structures 12A, 12B may be first moved from adeployed configuration (FIG. 3C) to a retracted configuration (FIG. 3B).Once the electrode structures 12A, 12B are retrieved into tubular member24, the entire nerve stimulation apparatus 10 may be withdrawn from thepatient's body. Alternatively, removing may not require retraction ofelectrode structure into the tubular member. Preferred methods forretrieving nerve stimulation apparatus 10 from the patient's body have anumber of advantages which include one or more of: (1) nerve stimulationapparatus 10 can be repositioned easily for replacement or if theelectrode moves with respect to target nerves, for example while thepatient is being moved or transferred; (2) periodic removal of nervestimulation apparatus prevents the build-up of plaques, or inflammation,or other undesirable physiological or pathological consequences as aresult of implanting nerve stimulation apparatus in a blood vessel; (3)nerve stimulation apparatus 10 can be conveniently removed from thepatient when nerve stimulation treatment is no longer needed.

Shaft portion 14 may take a number of different configurations. In theembodiment shown in FIG. 4A, a shaft portion 14A comprises a pair oftubes 14A1, 14A2 that are joined together in parallel. Tubes 14A1, 14A2may be welded or affixed in another suitable manner together at certainspaced apart points or continuously along their length. Tubes 14A1, 14A2may be made of stainless steel or other suitable material. The two-tubeconfiguration in FIG. 4A allows shaft portion 14A to bend more easily ina plane extending between the two tubes than in a plane of the twotubes.

In the embodiment shown in FIG. 4B, a shaft portion 14B comprises a pairof tubes 14B1, 14B2 that are coupled together in a concentric fashion.Tube 14B1 has a smaller diameter than tube 14B2 and is insertable andmovable in tube 14B2. Tube 14B1 is distal to tube 14B2. Tube 14B1 may bemore flexible than tube 14B2.

FIGS. 5A and 5B are schematic views of a nerve stimulation apparatus 10Caccording to an example embodiment of the invention (in a deployedconfiguration and a retracted configuration respectively). In the FIGS.5A and 5B embodiment, electrode structure 12AC is coupled to a distalend of shaft portion 14C, and electrode structure 12BC is coupled to amid-portion of shaft portion 14C. The coupling between electrodestructure 12B and shaft portion 14C may comprise a spring mechanism 35C.Electrode structure 12AC is retractable and extendable through a distalopening of tubular member 24C. Electrode structure 12BC is retractableand extendable through a side opening 34C of tubular member 24C.

FIGS. 6A and 6B are schematic views of a nerve stimulation apparatus 10Daccording to another example embodiment of the invention. In theembodiment shown in FIGS. 6A and 6B, nerve stimulation apparatus 10Dcomprises a first tubular member 24D and a second tubular member 36D.Electrode structure 12AD is coupled to a distal end of shaft portion14D. However, electrode structure 12BD is disposed on first tubularmember 24D. Also, first tubular member 24D passes through second tubularmember 36D and electrode structure 12BD is retractable into secondtubular member 36D. First and second tubular members 24D, 36D may beassembled in a telescoping fashion. Second tubular member 36D has adiameter greater than the diameter of first tubular member 24D. Secondtubular member 36D is typically shorter than first tubular member 24D.The position of electrode structures 12AD, 12BD may be controlledindependently from one another via shaft portion 14D and tubular member24D respectively.

FIGS. 7A and 7B are schematic views of a nerve stimulation apparatus 10Eaccording to another example embodiment of the invention. In the FIGS.7A and 7B embodiment, electrode structure 12AE is coupled to a shaftportion 14E1, and electrode structure 12BE is disposed on a shaftportion 14E2 which is separate from shaft portion 14E1. Shaft portion14E2 may be structurally different from shaft portion 14E1. Shaftportions 14E1, 14E2 may be independently controlled to deploy or retractelectrode structures 12AE, 12BE, respectively. Also, first tubularmember 24E passes through a second tubular member 36E. Electrodestructure 12AE is retractable into first tubular member 24E. Electrodestructure 12BE is retractable into second tubular member 36E. Secondtubular member 36E has a diameter greater than the diameter of firsttubular member 24E. Second tubular member 36E is typically shorter thanfirst tubular member 24E.

FIG. 8 schematically shows a nerve stimulation apparatus 10F accordingto another example embodiment of the invention. In the FIG. 8embodiment, electrode structure 12AF is coupled to a shaft portion 14F1,and electrode structure 12BF is disposed on a shaft portion 14F2 whichis separate from shaft portion 14F1. Shaft portion 14F2 may bestructurally different from shaft portion 14F1. Shaft portions 14F1,14F2 may be independently controlled to deploy or retract electrodestructures 12AF, 12BF, respectively. Tubular member 24F comprises asingle lumen 32F. Both shaft portions 14F1 and 14F2 extend inside lumen32F. Electrode structure 12AF may extend out of a distal opening oflumen 32F. Electrode structure 12BF may extend out of a side opening 34Fof tubular member 24F.

FIG. 9 schematically shows a nerve stimulation apparatus 10G accordingto another example embodiment of the invention. Apparatus 10G is similarto apparatus 10F except that tubular member 24G of apparatus 10Gcomprises two lumens 32G1 and 32G2. The two lumens 32G1 and 32G2 areseparated by a partition 33G. Shaft portion 14G1 extends in lumen 32G1and electrode structure 12AG extends out of a distal opening of lumen32G1. Shaft portion 14G2 extends in lumen 32G2 and electrode structure12BG extends out of a side opening 34G of lumen 32G2.

FIG. 10A is a side view of a nerve stimulation apparatus 10H accordingto an example embodiment of the invention. FIG. 10B is an isometric viewof apparatus 10H in combination with an introducer 38H and a hub 40H.FIGS. 10C, 10D are possible cross-sectional views of apparatus 10H.Nerve stimulation apparatus 10H comprises electrode structures 12AH,12BH, and a tubular member 24H.

Nerve stimulation apparatus 10H may be coupled to an introducer 38H anda hub 40H. This may be done during use to facilitate entry of the nervestimulation apparatus into a patient's blood vessel. It should be notedthat other types of introducers and/or hubs different from the onesshown in FIG. 10B may also be used in conjunction with nerve stimulationapparatus 10H. Electrode structure 12AH is connected to a shaft portion14H which extends inside tubular member 24H. Electrode structure 12BH isdisposed on first tubular member 24H. The distance between electrodestructure 12AH and 12BH may be in the range of 5-10 cm for example. Thedistance between electrode structure 12BH and the distal end ofintroducer 38H may be in the range of 0-5 cm for example.

Tubular member 24H is partially received in tubular member 36H ofintroducer 38H. When nerve stimulation apparatus 10H is applied to apatient, hub 40H and the wing portion of introducer 38H stay outside ofthe patient. Introducer 38H and/or hub 40H may comprise holes forsuture. In their deployed configuration, electrode structures 12AH and12BH have a transverse dimension that is greater than the transversedimension of tubular member 24H. Apparatus 10H comprises a thermistor64H or other temperature sensor.

Tubular member 24H may comprise a multi-lumen catheter. FIGS. 10C, 10Dshow possible cross sections of tubular member 24H. Tubular member 24Hmay have 1, 2, 3, 4, 5, or more lumens 32H. Shaft portion 14H and leads45H may run inside one or more of the lumens 32H. Leads 45H may also runinside the bore of shaft portion 14H.

FIGS. 11A and 11B show a nerve stimulation apparatus 10I in combinationwith an introducer 38I and a hub 40I according to an example embodimentof the invention. FIGS. 11C and 11D are cross sectional views of nervestimulation apparatus 10 along lines B-B and A-A respectively in FIG.11B. Nerve stimulation apparatus 10I comprises a first tubular member24I, a second tubular member 36I, an introducer 38I, a hub 40I, a firstelectrode structure 12AI, a second electrode structure 12BI, a firstshaft portion 14I (not visible) and a second shaft portion 68I (notvisible). Electrode structure 12AI is attached to a distal end of firstshaft portion 14I. First shaft portion 14I is visible in FIGS. 11C and11D (in cross section). Electrode structure 12AI is retractable into thedistal end of tubular member 24I. Electrode structure 12BI is attachedto second shaft portion 68I. Electrode structure 12BI is extendable outof the distal end of second tubular member 36I and is retractable intothe distal end of tubular member 36I. Second shaft portion 68I isvisible in FIG. 11C (in cross section). First tubular member 24I islonger than second tubular member 36I and passes through second tubularmember 36I. First tubular member 24I comprises a plurality of lumens32I, and second tubular member 36I surrounds the multi-lumen firsttubular member 24I. Because electrode 12AI and 12BI are attached to twoseparate shaft portions 14I and 68I, respectively, electrode structures12AI and 12BI can be independently controlled from outside the body.

FIG. 12 shows a nerve stimulation apparatus 10J according to an exampleembodiment of the invention. Apparatus 10J comprises a tubular member24J. Electrode structure 12AJ extends out of the distal end of tubularmember 24J whereas electrode 12BJ extends out of an opening 34J ontubular member 24J. Electrode structure 12AJ is attached to shaftportion 14J and electrode structure 12B is attached to shaft portion68J. Shaft portions 14J and 68J are both inside tubular member 24J.Electrode structures 12AJ and 12BJ can be independently controlled fromoutside the body.

FIG. 13A shows a nerve stimulation apparatus 10K. In this embodiment,tubular member 24K has five lumens 32K. FIGS. 13B-13E show some possiblecross sections of tubular member 24K taken at line A-A in FIG. 13A.Three lumens 32K may be used for drug infusion and are in fluidcommunication with openings 62AK, 62BK, 62CK located in a proximal,middle and distal portion of tubular member 24K. One lumen containsshaft portion 14K which is coupled to electrode structure 12AK. Onelumen contains shaft portion 68K which is coupled to electrode structure12BK. In FIG. 13B, each of the five lumens has the same size and has acircular cross section. In FIG. 13C, the lumens have different sizes,but all have circular cross sections. In FIG. 13D, the lumens havedifferent sizes and non-circular cross sections. In FIG. 13E, the lumenshave different sizes and are a mix of circular and non-circular crosssections.

FIG. 14A is another embodiment of a nerve stimulation apparatus 10L.FIGS. 14B and 14C show some possible cross sections of tubular member24L in the FIG. 14A embodiment. In the FIG. 14A embodiment, tubularmember 24L has three lumens 32L. One lumen 32L contains shaft portion14L which is coupled to electrode structure 12AL. One lumen 32L containsshaft portion 68L which is coupled to electrode structure 12BL. Onelumens may be used for drug infusion to opening 62L located in a middleportion of tubular member 24L. In FIG. 14B, each of the three lumens hasthe same size and has a circular cross section. In FIG. 14C, the lumenshave non-circular cross sections.

FIG. 15 shows a nerve stimulation apparatus 10M. Apparatus 10M comprisea tubular member 24M. The proximal end of tubular member 24M is coupledto introducer 38M. Introducer 38M has a side port 39M. Both electrodestructures 12AM, 12BM extend out of a distal opening of tubular member24M. Electrode structure 12AM is coupled to shaft portion 14M. Electrodestructure 12BM is coupled to shaft portion 68M. Electrode structures12AM and 12BM can be independently controlled.

FIG. 16 shows a nerve stimulation apparatus 10N. Nerve stimulationapparatus 10N comprises a tubular member 36N, an electrode structure 12Nand a shaft portion 14N (not visible). Electrode structure 12N extendsout of a distal opening of tubular member 36N. Shaft portion 14N isinside tubular member 36N. Tubular member 36N may be a cannula orcatheter-type tubular member. The length of tubular member 36N issufficiently long to enter the vessel by about 1 cm such that nervestimulation apparatus 10N is suitable for stimulating the left phrenicnerve when inserted into a patient's LSV and left BCV.

FIG. 17 shows a nerve stimulation apparatus 10O. Nerve stimulationapparatus 10O comprises a tubular member 24O, an electrode structure 12Oand a shaft portion 14O (not visible). Electrode structure 12O isattached to a distal end of shaft portion 14O. Shaft portion 14O is notvisible in FIG. 17 because shaft portion 14O is inside tubular member24O. Tubular member 24O may be a catheter-type tubular member. Thelength of tubular member 24O may be 16-20 cm so that nerve stimulationapparatus 10O is suitable for stimulating the right phrenic nerve wheninserted into a patient's LSV, left BCV and then enters SVC. It shouldbe noted that apparatus 10N, 10O may be used in combination to stimulateboth left and right phrenic nerves at the same time.

FIGS. 18A, 18B show an electrode structure 12P according to an exampleembodiment of the invention. FIG. 18A is a top plan view of electrodestructure 12P. FIG. 18B is a bottom perspective view of electrodestructure 12P. Electrode structure 12P comprises at least one electrode20P and an insulating pad 42P. Pad 42P may be resiliently flexible. Whenelectrode structure 12P is not confined inside a tubular member, pad 42Pcan automatically spring open to take a desired shape. When electrodestructure 12P springs open, electrode structure 12P may have a dimensionthat is greater than the transverse dimension of the tubular member. Toretrieve electrode structure 12P into a tubular member, electrodestructure 12P can be collapsed and/or pulled back into the tubularmember by pulling shaft portion 14P which is coupled to electrodestructure 12P. Electrode 20P may be supported on pad 42P, but this isnot mandatory. Pad 42P has a petal or leaf-like shape, although pad 42Pmay be of any other suitable shape. Pad 42P may be an insulating pad,thereby insulating electrode 20P from the blood in a blood vessel. Pad42P may be made of an insulating material or materials. Suitablematerials for making pad 42P include, without limitation, PTEF,silicone, PET, and nylon. Pad 42P may present a high-impedance to theflow of electrical current and therefore reduces the amount of currentflowing through the blood when electrode structure 12P is deployed in ablood vessel.

It is not mandatory that pad 42P have an extremely high electricalresistance. It is sufficient if pad 42P has a resistance to the flow ofelectricity through pad 42P that is significantly greater than thatpresented by the blood in blood vessel V. Blood typically has aresistivity of about 120 to 190 Ωcm. In example embodiments, the bloodin a blood vessel may provide an electrical resistance betweenclosely-spaced electrical contacts that is inversely proportional to thedimensions of the lumen of the blood vessel. In large blood vessels thelongitudinal electrical resistance between reasonable closely-spacedcontacts can be a few tens of ohms for example. Pad 42P preferablyprovides an electrical resistance of at least a few hundred ohms,preferably a few kilo ohms or more to the flow of electrical currentthrough the thickness of pad 42P. Pad 42P could have electricallyconductive members such as leads and the like embedded within it orelectrically-conductive electrode or other features on its inner surfaceand still be considered to be ‘insulating’.

For example, electrode 20P may be supported on pad 42P. Pad 42P can berolled up and retracted into the tubular member to facilitate insertionor retrieval of electrode structure 12P within a blood vessel. Whenelectrode structure 12P is deployed, pad 42P can spring open to take ashape that has a curvature that generally conforms to the wall of ablood vessel. This helps to bring electrode 20P which is on a side ofpad 42P to be in close proximity of the blood vessel wall. Blood flow inthe blood vessel may also assist in deploying electrode structure 12Pand pressing pad 42P against the walls of a blood vessel. It should benoted that electrode structure 20P does not need to be fixed or fastenedto the blood vessel wall, but rather can float inside the blood vesselagainst the wall.

In the embodiment of FIGS. 18A, 18B, electrode structure 12P alsocomprises a wire 44P which is connected to shaft portion 14P. Wire 44Ppasses through apertures 46P in pad 42P, thereby holding pad 42P inplace. Wire 44P may provide structural support to pad 42P. Additionally,wire 44P may optionally serve as a ground electrode or a referenceelectrode. In FIG. 18B, a lead 45P extends from a bore in shaft portion14P to a backside 56P of electrode 20P. Lead 45P may be coated with aninsulating material (e.g., Teflon™ or other suitable insulatingmaterial). Sensors such as a thermistor, an oxygen sensor, and/or CO₂sensor (not shown) may be supported on electrode structure 12P. In someembodiments, electrode structures 12P may be used for plethysmography.

In the illustrated embodiment, electrode 20P is exposed on one side(e.g., the convex side, i.e., the side facing the blood vessel wall) ofpad 42P. Pad 42P may, for example, comprise a reinforced siliconematerial. In one embodiment, pad 42P is a pad of Dacron-mesh-reinforcedsilicone. This material can be rolled up, has shape memory so that ittends to open up, and is resiliently flexible so that it can conform tothe wall of a blood vessel. Blood flow in the blood vessel may alsoassist in deploying electrode structure 12P and supporting electrodestructure 12P against the walls of a blood vessel.

FIG. 19A shows a schematic of a cross section of an electrode structure12Q according to one example embodiment of the invention. In FIG. 19Aembodiment, electrode 20Q comprises one or more ribbons 48Q of asuitable biocompatible metal. Pad 42Q on which the ribbons 48Q aresupported comprises two layers. A top layer 50Q which faces the wall ofthe blood vessel has apertures 52Q and the ribbons 48Q pass throughaperture 52Q such that a portion of the ribbons 48Q is exposed and ableto contact or be in close proximity of a wall 54Q of the blood vessel.This is schematically shown in FIG. 19B. The bottom layer 56Q whichfaces the center of the blood vessel may be made of a suitableinsulating material. Ribbons 48Q are electrically coupled to lead 45Qwhich is directly or indirectly coupled to a source of electricity(e.g., a stimulation generator). The bottom insulating layer 56Q maycomprise a thin material such as Teflon™, polyurethane, or silicone.

The material of electrode 20Q is preferably relatively thin so that itdoes not make the electrode structure too stiff. For example, theelectrode material may comprise metal ribbons 48Q that are 0.5 to 1 mmwide, or less than 0.5 mm wide. In other embodiments the electrodes maycomprise areas of conductive polymer printed on or contained in theinsulating material of the electrode structure.

Generally, the delivery of electrical stimulation to a target nerve isenhanced by:

-   -   locating electrode 20 against the internal wall of the blood        vessel at a location close to the target nerve;    -   providing electrode 20 having a relatively large contact surface        that can achieve a large contact area with the internal wall of        the blood vessel;    -   curving the contact surface of electrode 20 to roughly match the        curvature of the inner face of blood vessel; and/or providing        insulating pad 42.

Experiments conducted by the inventors have shown that it is possible toachieve a similar level of stimulation of a target nerve using insulatedelectrodes by applying only one third of the electric current ascompared to using uninsulated electrodes. The reduced electric currentcan result in less damage to tissues within a patient as well as a lowerrisk of unintended stimulation. Additionally, selectivity for a targetnerve is improved. Low current and high selectivity for a target nerveis advantageous because it avoids activating non-target nerves which maybe close by. For example, it is known that the vagus nerve is typically2-3 cm medial with respect to the phrenic nerves in humans.

FIGS. 20A and 20B are perspective and side views of wire 44P accordingto one example embodiment. Wire 44P is connected to shaft portion 14P.Wire 44P may form a hair-pin configuration, extending from shaft portion14P on one side of pad 42P (not shown in FIGS. 20A and 20B), passingthrough apertures 46P in pad 42P to the other side of pad 42P and thenextending in the opposite direction.

Where shaft portion 14P comprises stainless steel tube(s), the wire 44Pmay, for example, be welded or otherwise attached to the stainless steeltube(s). Wire 44P may comprise a loop of 0.010 inch stainless steel (forexample Elgiloy™). The wire of the loop may pass through apertures 46Pin the insulating pad 42P on which electrode(s) 20P are supported asshown in FIGS. 18A, 18B. This positively retains pad 42P in place. Wire44P may be passed through apertures 46P before being affixed to shaftportion 14P. In some embodiments, wire 44P provides one of a pluralityof electrodes for monitoring bioelectrical activity and/or deliveringelectrical stimulation.

FIGS. 21A, 21B are top and bottom perspective views of an electrodestructure 12R. Electrode structure 12R is similar to electrode structure12P. In FIGS. 21A, 21B, pad 42R is flexible and partially rolled-up, andelectrode 20R is located on the convex side of pad 42R.

FIG. 22 shows an electrode structure 12S according to one exampleembodiment. As shown in FIG. 22, pad 42S of electrode structure 12S isasymmetrical. This provides better coverage and provides the possibilityof placing the electrodes 20S at more discrete locations around a bloodvessel while still being able to compactly roll up the electrodestructure 12S for insertion and retrieval. A plurality of electrodes 20Sare provided on electrode structure 12S. Providing a plurality ofelectrodes 20S on each electrode structure allows selection of anelectrode or a combination of electrodes to provide the most effectivestimulation of a target nerve.

FIGS. 23A-23E show how an example electrode structure 12T may be rolledup and retracted into a tubular member 24T. In FIGS. 23A-E, pad 42T ofelectrode structure 12T is flexible enough that electrode structure 12Tcan be pulled into tubular member 24T by pulling shaft portion 14T (notvisible) which is coupled to electrode structure 12T.

FIGS. 24A-24E show how an example electrode structure 12U may be rolledup, deployed, and retracted into a tubular member 24U. As shown in FIG.24A, electrode structure 12U may initially be fully rolled up insidetubular member 24U (e.g., when nerve stimulation apparatus 10 is beinginserted into a patient's blood vessel). The two halves of pad 42U ofelectrode structure 12U may be rolled up in the same direction.

As shown in FIGS. 24B and 24C, when nerve stimulation apparatus 10 islocated in a desired position in the patient's blood vessel, electrodestructure 12U may be deployed by moving electrode structure 12U out oftubular member 24U and opening pad 42U. As shown in FIGS. 24D and 24E,electrode structure 12U may be retrieved by turning or rotating shaftportion 14U from outside the body to roll up pad 42U. Once pad 42U isrolled up, electrode structure 12U can be retrieved into tubular member24U. The entire tubular member 24U which contains electrode structure12U can then be withdrawn from the patient's body.

FIGS. 25 and 26 show two example electrode structures 12V, 12W. The FIG.25 electrode structure 12V has a pad 42V that has a gentle curl (incross section). Electrodes 20V are located on a convex side of pad 42V.Pad 42V comprises a low-stiffness spring wire loop 70V. In FIG. 25, wireloop 70V is in its relaxed, expanded configuration. Wire loop 70V may bemade of nitinol or stainless steel, for example. Wire loop 70V may belocated on the side of pad 42V that is facing the center of the bloodvessel (e.g., the concave side of pad 42V) and opposite from the sidewhere electrodes 20V are located. Alternatively, wire loop 70V may besandwiched inside a pocket formed by two insulating pad layers of pad42V. Electrodes 20V are exposed on the side of pad 42V that is facingthe wall of the blood vessel (e.g., the convex side of pad 42V). Wire44V is woven and adhered to pad 42V to provide structural support andstiffness to pad 42V. Electrode structure 12V may be withdrawn intotubular member 24V by pulling on shaft portion 14V from outside thebody. On reaching the edge of tubular member 24V, the low stiffnessdeformable spring wire loop 70V collapses and pad 42V enters tubularmember 24V. The tubular member 24V together with electrode structure 12Vis then withdrawn from the body.

The FIG. 26 electrode structure 12W is similar to the FIG. 25 electrodestructure 12V except that wire loop 70V is replaced with deformablelow-stiffness springy ribs 72W. Electrode structure 12W may be retrievedinto tubular member 24 in a similar fashion as electrode structure 12V.

FIGS. 27A-27E schematically illustrate a nerve stimulation apparatus 10Xaccording to another embodiment. FIG. 27A shows apparatus 10X coupled toa hub 40X. FIG. 27B shows apparatus 10X in position inside left BCV andSVC. Apparatus 10X comprises electrode structures 12AX, 12BX(collectively 12X). Electrode structures 12AX, 12BX may be the same orcan be of different sizes and/or shapes. As shown in FIG. 27C, pad 42Xof each electrode structure 12X comprises an inflatable balloon 58X. Theinflatable balloon 58X may be made of a suitable polymer material (e.g.,PET, nylon, silicone). The balloon 58X may be compliant, semi-compliant,or non-compliant. The balloon 58X may be inflated with a fluid (e.g,saline solution) and, once inflated, will take the desired shape.Electrodes 20X are disposed on one side of pad 42X. Electrodes 20X maybe printed or glued on balloon 58X. Apparatus 10X also comprises aconduit for infusing fluid into balloon 58X, and the infusion of fluidinto balloon 58X can be controlled from outside the body. FIG. 27D showselectrode structure 12X with balloon 58X in a deflated state. FIG. 27Eshows electrode structure 12X with balloon 58X in a inflated state. Outof the package, balloon 58X is pleated and folded to wrap around shaftportion 14X. Balloon 58X is parked inside one of the lumens of apparatus10X. To deploy electrode structure 12X, shaft portion 14X is pushed fromthe proximal end of apparatus 10X; balloon 58X pops out of an opening oftubular member 24X and then is inflated. To retrieve balloon 58X,balloon 58X is first deflated and then pulled into one of the lumens ofapparatus 10X from the proximal end of apparatus 10X via shaft portion14X.

FIGS. 28A, 28B show an example method for locating electrode structure12 in a blood vessel V to a target nerve N. In this method, electrodestructure 12 is inserted into blood vessel V while electrode structure12 is retracted within tubular member 24. Electrode structure 12 is thenextended out of tubular member 24 and positioned at location A. At thispoint, the amount of electric current required to stimulate nerve N ismeasured using a suitable device. This may be done, for example, bydetecting muscle activity as a result of nerve stimulation, for example,diaphragm muscle activity as result of phrenic nerve stimulation.Electrode structure 12 is then retracted into tubular member 24. Thentubular member 24 is advanced in blood vessel V for a small distance(e.g., 0.1 mm, 0.2 mm, 0.5 mm, 1 mm, 2 mm, 5 mm, etc.) and electrodestructure 12 is then extended out of tubular member 24 and positioned atLocation B. Again, the amount of electric current required to stimulatenerve N is measured using a suitable device. These steps are repeated(e.g. at Location C, Location D, Location E) for as many times asnecessary.

By making a set of such measurements, one can obtain a functionindicating how the amount of electric current required to stimulatenerve N varies in relation to the position of electrode structure 12along blood vessel V. FIG. 28B shows a schematic graph of such afunction. In this graph, the amount of electric current required tostimulate nerve N is the lowest at Location C. Therefore, in thisillustration, Location C is a desirable or optimal location to placeelectrode structure 12 as compared to Locations A, B, D and E. Thismethod can be practised either manually or in conjunction with asuitable machine, such as a graphing calculator or a computer.

One aspect of the invention relates to sensors for sensing and/ormonitoring the position of an electrode structure 12 inserted into ablood vessel and associated methods. The sensor may be optionallydisposable. The sensor may be placed outside of the patient's body. Thesensor may be fixed to the reference frame of the patient's body. As anelectrode structure 12 is advanced and/or rotated in a blood vessel by atherapist, the sensor acquires positional data and can also relay datato a control unit where electrode position is monitored simultaneouslywith stimulation parameters and results of stimulation. The control unitcalculates the best placement of electrodes 20 and can store thisinformation or provide feedback to the therapist in real time or atlater times.

A nerve stimulation system according to an embodiment of the presentinvention may comprise the following: an intravascular nerve stimulationapparatus having flexible tubular member(s) that can be inserted,advanced, and/or rotated in a blood vessel; one or more sensors thattrack the position of the intravascular electrodes; and a control unitthat acquires position data and relays it to the therapist and/or storesit for later use. Typically, the sensor is coupled to a proximal part ofa shaft portion of the nerve stimulation apparatus. The sensor may beplaced outside of the body.

FIG. 29A schematically shows an example embodiment of a sensor 80A thatis independent from an introducer or tubular member of an intravascularnerve stimulation apparatus 10. FIG. 29B schematically shows an exampleembodiment of a sensor 80B that is integrated with an introducer ortubular member of an intravascular nerve stimulation apparatus 10.

In some embodiments, the sensor is a pressure-sensitive variableresistance potentiometer sensor. Such a sensor is suitable formonitoring the position (depth) of an intravascular electrode inside ablood vessel. The sensor supplies a voltage output signal that isapproximately linearly proportional to the position of the electrode.FIGS. 29C and 29D show an example sensor 80C in cross-sectional andperspective views. Sensor 80C comprises a pressure-sensitive linearpotentiometer 81. A low-friction bead 82C (e.g., a Teflon bead) is fixedonto an elongate shaft portion 14. Potentiometer 81, bead 82, and partof shaft portion 14 are assembled within a guide chamber 84C to formsensor 80C. Sensor 80C may be fixed either to the patient, or to thetubular member or the introducer of a nerve stimulation apparatus. Asthe shaft portion 14 advances, the bead 82 slides along and exertspressure on potentiometer 81, therefore changing its resistance. Thepoint of contact of the bead 82 against the potentiometer 81 provides asignal that, provided that the shaft portion 14 does not buckle, isgenerally linearly proportional to the intravascular position of theelectrode 20.

The length of the active region of the potentiometer 81 limits thedistance over which the depth of the electrode 20 can be tracked. Insome embodiments, a commercially available flexible potentiometer may beused with a 6 cm long active region which is sufficient to monitor themovement of an electrode in the vicinity of its target phrenic nerve.However, potentiometers of any desired length may be manufactured forthis purpose. If shaft portion 14 has a circular cross-section and bead82 is spherical and coaxial the shaft portion 14, the shaft portion 14can be rotated while maintaining contact with the potentiometer 81 toobtain the angular positions of the shaft portion 14 and electrode 20.FIGS. 29F-H show an additional example embodiments of sensor 80D,wherein the guide chamber 84D has a generally triangular cross-section.

In some embodiments, sensor 80 is integrated with the hub of a nervestimulation apparatus. An example sensors 80G is shown in FIG. 29L. Thedepth and the angular position of an intravascular electrode can bemonitored by combining the use of a linear potentiometer as describedabove, plus a circular potentiometer to monitor rotation of the shaftportion. Alternatively, the angular position can be controlled by aseries of “click stops” placed at convenient angles (e.g., one stopevery 15° or 30°) over a desired angular range (e.g., +/−90° from acentral default angular position of an electrode) and a multi-poleelectrical switch can be connected to indicate each click stop. Tomonitor rotation of the shaft portion, the shaft portion proximal to thelinear transducer can be modified to be of non-circular cross-section,for example square cross-section, and a dial can be incorporated with asquare hole through which the shaft portion travels. The therapist canmanually rotate either the shaft portion itself or its associated dial,and the rotational movement of the dial is sensed by an integratedsensor housed inside the hub of the nerve stimulation apparatus oralternatively by a multi-pole electrical switch with pre-set clickstops. FIG. 29L shows an embodiment wherein the shaft portions 14 can berotated by dials.

FIG. 29M shows an embodiment of a sensor 80H in which the shaft portion14 is coupled by way of a string or other flexible element to aspring-loaded shaft fitted with a rotational sensor 90. The rotationalsensor's rotational axis 91 is fitted with a rotational encoder (notshown in FIG. 29M), which can be converted into a linear displacementmeasurement. The shaft portion 14 is attached to rotational sensor 90using a collar 92 and a wire 94. As the shaft portion 14 is moved, thecollar 92 slides through a guide 96 which prevents the shaft portion 14from moving in any axis other than the one in which the rotationalsensor 90 keeps track of position. To make the assembly smaller,rotational sensor 90 may be put at an angle by having the wire 94redirected by a pulley or a block 98. To move the shaft portion 14, thecollar 92 can be fitted with a slider or the assembly can allow the userto move the shaft portion 14 directly.

FIGS. 29N and 29O are side and front views of a sensor 80J where theshaft portion 14 is fitted between a roller 100 and a guide 102. As theshaft portion 14 passes the roller 100, it creates a rotational motionof the roller 100 in the same direction. The rotational movement of theroller 100 is then converted to a linear movement through an encoder104. Both roller 102 and encoder 104 are located co-axially on arotational axis 106.

FIG. 29P shows a sensor 80K wherein shaft portion 14 is fitted with acollar 108 made out of an insulating material. The collar 108 has atleast one conductive ring 110. Ring 110 slides through a guide 112fitted with electrical contacts 114. As the collar 108 slides throughthe guide 112 and the ring 110 touches the electrical contacts 114 oneach side, a current passes through the ring 110. The current may beconverted to positional data, either by correlating position toresistance or by identifying the shorted contacts and associating themwith a calibrated position.

FIG. 29Q shows a sensor 80L in which a shaft portion 14 is fitted withtwo resistive traces 116 connected at one end. Both resistive traces 116are exposed, but the bridge connecting them is not. As the shaft portion14 slides into ring guide 118, both traces 116 contact two halves of ametallic ring. A current is sent through one half, and received via theother half. The current goes through the traces 116 on the shaft portion14. The voltage drop measured across the ring halves is proportional tothe length of the traces 116 the current goes through. By calibratingthe resistance, a position measurement can be obtained.

One or more angle sensors may be used with the apparatus describedherein. FIG. 30A shows an example angle sensor 200 (in side view) inwhich a lead with a non-circular profile slides through a disc which isfree to rotate. Angle sensor 200 comprises wiper 202 (FIG. 30B) andpotentiometer 204 (FIG. 30C). When the lead is rotated, the sleeverotates with the wiper 202 that applies a pressure on cylindricalmembrane potentiometer 204.

FIGS. 30D to 30F shows an example angle sensor 208 in which a lead witha non-circular profile slides through a sleeve 210 which is free torotate. FIG. 30D is a cross-sectional view of sensor 208. FIG. 30E is aside view of sensor 208. FIG. 30F is an exploded view of sensor 208.When the lead is rotated, the sleeve 210 rotates with a wiper part 211that applies a pressure on a potentiometer. Sensor 208 comprises sleeve210 with wiper 211, conductive membrane 212, space layers 214, resistivetrace 216 and support structure 218.

FIGS. 30G and 30H show an angle senor 220 in which a lead withnon-circular profile slides through a sleeve which is free to rotate.Sensor 220 comprises sleeve 222 having a conductive strip 224, aflexible PCB 226, and a support structure 228. The flexible PCB 226comprises electrical contacts 234, measurement traces 232, and aperpendicular trace 230. When the lead is rotated, the sleeve 222rotates and creates an electrical contact with a cylindrical board withmultiple contacts. This part may be a flexible PCB 226 with a series ofparallel exposed traces 232 and one perpendicular trace 230. Theperpendicular trace is then energized and shorted with one of the othertraces via a conductive strip on the rotating sleeve. A control unitthen cycles through the contacts and looks for the traces that areenergized to find the position. The conductive part shorting the tracescan be shorting only the energized trace with another, or more than one.For example, the conductive part could short all traces but one, so thatthe control unit would look for the trace that is not energized.

FIGS. 31A-31D show a “cobra hood” expandable design which may be used incombination with the electrode structure of the nerve stimulatingapparatus described herein as well as in other contexts. Such a designmay be used, for example, to provide a backing member (e.g., petal) forone or more electrodes. For example, such a structure may be deployed tostimulate the left phrenic nerve. FIG. 31B is a schematiccross-sectional view of the cobra design wherein an expandable shroud302 is in an unexpanded configuration. FIG. 31C is a schematiccross-sectional view of the cobra design wherein shroud 302 is in anexpanded configuration. FIG. 31D is a schematic plan view of the cobradesign wherein shroud 302 is in an unexpanded configuration. FIG. 31E isa schematic plan view of the cobra design wherein shroud 302 is in anexpanded configuration.

Shroud 302 comprises a panel of material. The material is electricallyinsulating. In some embodiments the material is elastically stretchable.When shroud 302 is not deployed, shroud 302 is configured to be storedinside a tubular member 306 in an unexpanded configuration. One or moreelectrodes 304 may be located above or on top of shroud 302, orientedtowards an inner surface of a blood vessel V.

Shroud 302 may be connected to and/or supported by a pair of flexiblemembers such as rods or tubes 308 which run inside tubular member 306when shroud 302 is not deployed. The flexible members may be resilientlyflexible. Rods or tubes 308 may be made of stainless steel, Nitinol, orsome other suitable material, for example. The distal ends of rods ortubes 308 may be anchored or fixed to tubular member 306 at anchorpositions 310. In alternative embodiments, distal ends of rods or tubes308 may move freely to some extent along the tubular member 306. Tubularmember 306 comprises side openings 312.

Shroud 302 can be manipulated from outside the body to move between acollapsed configuration and an expanded configuration. When a userpushes the proximal ends of rods or tubes 308 towards the distal ends,portions of rods or tubes 308 along side openings 312 bulge out andextend out of side openings 312 of tubular member 306. This in turnstretches shroud 302 to open to an expanded configuration. When shroud302 is expanded, it forms a petal-like backing member for electrodes304. Shroud 304 may help to position electrodes 304 against the bloodvessel wall. The electrically insulating shroud also functions as anelectrically insulating backing sheet which helps to insulate electrodes304 from the blood flowing in the lumen of the blood vessel.

To return shroud 302 into tubular member 306, the force applied to rodsor tubes 308 is released. Rods or tubes 308 are returned to a straightconfiguration and retrieved into tubular member 306. This in turn bringsshroud 302 into a collapsed configuration inside tubular member 306.

The “cobra” design shown in FIGS. 31A-31E may be altered to produce a“half cobra” design. In a “half cobra” design, one edge of shroud 302 isconnected to and/or supported by a rod or tube 308; the other edge ofshroud 302 is fixed inside tubular member 306 (e.g., fixed to an insidesurface of tubular member 306). When rod or tube 308 is manipulated tobulge out, shroud 302 expands to one side to form a “half cobra” backingsheet in an expanded configuration. A device may comprise two “halfcobra” shrouds side by side which together form a “full-cobra” backingsheet in operation.

Electrodes 304 could be located on tubular member 306. Instead of or inaddition to electrodes 304 on tubular member 306, electrodes 304 couldbe on shroud 302. Where flexible members 308 are electricallyconductive, portions of flexible member 308 may be exposed to provideelectrodes.

The applications of the apparatus and methods described herein are notlimited to phrenic nerves. The apparatus and methods described hereinmay be applied to provide surgically simple, low risk solutions forstimulating a wide range of peripheral or cranial nerves. For example,the methods and apparatus may be applied to stimulate the obturatornerve in the hip/groin area or the trigeminal nerve in the head.

The apparatus and methods may be applied to treatment of a wide varietyof disorders such as pain of peripheral or craniofacial origin, sensorydeficits, paralysis or paresis of central origin, autonomic disorders,and generally any medical condition that can be treated or alleviatedusing neuromodulation by electrical stimulation of a nerve that is inclose proximity to a blood vessel into which a nerve stimulationapparatus can be deployed.

Various elements of the invention may be used alone, in combination, orin a variety of arrangements not specifically discussed in theembodiments described in the foregoing. For example, elements describedin one embodiment may be combined with elements described in otherembodiments to yield further example embodiments.

The scope of the invention should not be limited by the embodiments setforth in the examples, but should be given the broadest interpretationconsistent with the description as a whole.

What is claimed is:
 1. A nerve stimulation system, comprising: acatheter including at least one lumen configured to remove a fluid froma patient or deliver a fluid to the patient; a plurality of distalelectrodes supported by the catheter, wherein the plurality of distalelectrodes are configured for stimulating a phrenic nerve; a pluralityof proximal electrodes supported by the catheter; and an electrodeassembly including a metal ribbon and an insulative layer, wherein theplurality of distal electrodes, the plurality of proximal electrodes, orboth, include an electrode configured to monitor the patient; andwherein the metal ribbon is electrically connected to at least oneelectrode, of the plurality of distal electrodes and plurality ofproximal electrodes, radially outward of the insulative layer.
 2. Thenerve stimulation system of claim 1, wherein the plurality of distalelectrodes are configured for stimulating a right phrenic nerve, and theplurality of proximal electrodes are configured for stimulating a leftphrenic nerve.
 3. The nerve stimulation system of claim 1, wherein oneor more electrodes of the plurality of distal electrodes, the pluralityof proximal electrodes, or both, is disposed on a polymer materialextension.
 4. The nerve stimulation system of claim 1, wherein the atleast one lumen is a first lumen, and the catheter further comprises oneor more additional lumens.
 5. The nerve stimulation system of claim 1,wherein the insulative layer is a top insulative layer, the electrodeassembly further includes a bottom insulative layer, and a portion ofthe metal ribbon is between the top insulative layer and the bottominsulative layer.
 6. The nerve stimulation system of claim 5, whereinthe bottom insulative layer is comprised of Teflon™, polyurethane, orsilicone.
 7. A nerve stimulation system, comprising: a catheterincluding at least one lumen; a distal electrode assembly including aplurality of distal electrodes supported by the catheter; and a proximalelectrode assembly including a plurality of proximal electrodessupported by the catheter; wherein the distal electrode assembly, theproximal electrode assembly, or both, include a metal ribbon; andwherein the plurality of distal electrodes, the plurality of proximalelectrodes, or both, is configured for stimulating a phrenic nerve, andwherein a portion of the metal ribbon is between a top insulative layerand a bottom insulative layer.
 8. The nerve stimulation system of claim7, wherein the metal ribbon has a width less than 0.5 mm.
 9. The nervestimulation system of claim 7, wherein the metal ribbon is electricallyconnected to at least one electrode above the top insulative layer. 10.The nerve stimulation system of claim 7, wherein an aperture of the topinsulative layer includes metal and the metal connects the metal ribbonto at least one electrode.
 11. The nerve stimulation system of claim 7,wherein the bottom insulative layer is comprised of Teflon™,polyurethane, or silicone.
 12. A nerve stimulation system, comprising: acatheter including at least one lumen; an electrode assembly including aplurality of electrodes, a metal ribbon, and an insulative layer; andwherein at least a portion of the plurality of electrodes is configuredfor stimulating a phrenic nerve; and wherein an aperture of theinsulative layer includes metal and the metal connects the metal ribbonto at least one electrode of the plurality of electrodes.
 13. The nervestimulation system of claim 12, wherein the insulative layer is a topinsulative layer, the electrode assembly further includes a bottominsulative layer, and a portion of the metal ribbon is between the topinsulative layer and the bottom insulative layer.
 14. The nervestimulation system of claim 13, wherein the bottom insulative layer iscomprised of Teflon™, polyurethane, or silicone.
 15. The nervestimulation system of claim 13, further comprising a polymer materialextension disposed on an exterior of the catheter, wherein one or moreelectrodes of the plurality of electrodes is disposed on the polymermaterial extension.
 16. The nerve stimulation system of claim 15,wherein the polymer material extension comprises one or more layers ofpolymer material.
 17. The nerve stimulation system of claim 12, whereinthe catheter is more flexible in a first direction than in a seconddirection.
 18. The nerve stimulation system of claim 12, wherein atleast one electrode of the plurality of electrodes is a printedelectrode.
 19. The nerve stimulation system of claim 12, wherein atleast one electrode of the plurality of distal electrodes or theplurality of proximal electrodes is configured to monitor a patient. 20.The nerve stimulation system of claim 12, wherein the at least one lumenis configured to remove a fluid from a patient or deliver a fluid to thepatient.
 21. The nerve stimulation system of claim 12, wherein thecatheter is configured to be inserted into a blood vessel.